Dendritic Cells Route Human Immunodeficiency Virus to Lymph Nodes after Vaginal or Intravenous Administration to Mice

Abstract

We have developed a murine model to study the involvement of dendritic cells (DC) in human immunodeficiency virus (HIV) routing from an inoculation site to the lymph nodes (LN). Murine bone marrow-derived DC migrate to the draining LN within 24 h after subcutaneous injection. After incubation of these cells with heat-inactivated (Hi) HIV type 1 (HIV-1), HIV RNA sequences were detected in the draining LN only. Upon injection of DC pulsed with infectious HIV, the virus recovered in the draining LN was still able to productively infect human T cells. After a vaginal challenge with Hi HIV-1, the virus could be detected in the iliac and sacral draining LN at 24 h after injection. After an intravenous challenge, the virus could be detected in peripheral LN as soon as 30 min after injection. The specific depletion of a myeloid-related LN DC population, previously shown to take up blood macromolecules and to translocate them into the LN, prevented HIV transport to LN. Together, our data demonstrate the critical role of DC for HIV routing to LN after either a vaginal or an intravenous challenge, which does not require their infection. Therefore, despite the fact that the mouse is not infectable by HIV, this small animal model might be useful to test preventive strategies against HIV.

When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses

“…Siglec-1 allows transferring viruses to bystander CD4 + T cells in the mucosa, but also the systemic viral dissemination upon DC migration to lymphoid tissues (Figure 4). Indeed, DCs bearing retroviruses are found in the draining lymph nodes of distinct animal models as soon as 24 h after vaginal challenge [12,[145][146][147] and these findings originally led to formulation of the Trojan Horse hypothesis, which states that DCs can serve as vehicles transporting the virus from the entry sites to distant tissues [9,10]. .…”

The influence of cytokines, chemokines and their receptors on HIV‐1 replication in monocytes and macrophages

“…However, in all DC subsets, especially in mature DCs, explosive levels of viral replication are induced when cocultured with CD4 lymphocytes [25,26]. Epithelial DCs capture (or are infected with) HIV-1 in peripheral tissues and transport the virus to lymph nodes, thus infecting activated CD4 T lymphocytes [16,17,[26][27][28]. DCs express surface receptors including the C-type lectins, langerin, mannose receptor and DC-specific ICAM-3 grabbing nonintegrin (DC-SIGN) which may interact with HIV-1 envelope glycoprotein, gp120 [29][30][31][32] and mediate viral internalisation.…”

Role of gp120 in dendritic cell dysfunction in HIV infection

“…Supporting this theory, there is growing experimental evidence of the capacity of some viruses, including HIV-1, to affect DC biology [2,3]. DCs are among the first cellular targets of HIV-1 [4 -7], and their migratory nature makes them strong candidates for viral spreading and transmission, either as directly infected cells or by passively transporting viruses sequestered in endosomal compartments [4,7,8]. Finally, DCs in lymphoid tissues may serve as reservoirs of HIV-1 that continually contribute to infection of newly recruited T cells [9].…”